Comprehensive Hearing Loss and Deafness Panel

  • bpg-method PLUS
  • bpg-method SEQ
  • bpg-method DEL/DUP

Test code: EA0501

The Blueprint Genetics Comprehensive Hearing Loss and Deafness Panel is a 158 gene test for genetic diagnostics of patients with clinical suspicion of Alport syndrome, branchio-oto-renal (BOR) syndrome, non-syndromic genetic deafness, Pendred syndrome, sensorineural hearing loss, unilateral and bilateral, Stickler syndrome, Usher syndrome or Waardenburg syndrome.

Hearing loss is a genetically and clinically heterogenous group of diseases and syndromes and may be classified in several different ways. This Panel includes comprehensively genes associated with both syndromic and non-syndromic hearing loss. In addition to protein coding regions, two disease causing intronic variants of HGF gene are targeted in this Panel. Inheritance of these disorders may be autosomal recessive or dominant as well as X-linked. This comprehensive Panel includes Waardenburg Syndrome Panel, Pendred Syndrome Panel, Usher Syndrome Panel, Stickler Syndrome Panel, Alport Syndrome Panel, Branchio-Oto-Renal Panel, Syndromic Hearing Loss Panel and Non-Syndromic Hearing Loss Panel.

About Hearing Loss and Deafness

Hearing loss is a genetically very heterogenous group of phenotypes varying in severity and causes. Non-syndromic sensorineural hearing loss is a partial or total loss of hearing that occurs in isolation, without other associated medical disorders. In syndromic hearing loss, symptoms affecting other parts of the body occur interlinked with hearing impairnment or deafness. Sensorineural hearing loss can be unilateral or bilateral and it can be stable or progressive. In addition, the loss may appear with various intensivity to high, middle or low tones. Some 75%-to-85% of congenital hereditary hearing impairnment have non-syndromic origin, while the remaining 15%-to-25% is syndromic in origin. The prevalence of non-syndromic hearing loss is 3-4:10000 neonates and increases with age. In many populations, mutations in GJB2 are the most prevalent explaining up to 50% of all non-syndromic hearing losses. Altogether syndromic hearing loss accounts for 20% to 30% of congenital hearing loss and deafness and the combined prevalence of syndromic hearing loss is approximately 1-2:10000.


Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more:

Genes in the Comprehensive Hearing Loss and Deafness Panel and their clinical significance
Gene Associated phenotypes Inheritance ClinVar HGMD
ABHD12 Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract AR 12 18
ACTG1* Deafness, Baraitser-Winter syndrome AD 21 43
ADCY1 Deafness AR 1 1
ADGRV1 Usher syndrome AR/Digenic 58 164
ALMS1* Alström syndrome AR 50 291
ANKH Calcium pyrophosphate deposition disease (familial chondrocalcinosis type 2), Craniometaphyseal dysplasia autosomal dominant type AD 12 20
ATP6V1B1 Renal tubular acidosis with deafness AR 9 54
BCS1L Bjornstad syndrome AR 32 37
BDP1* Hearing loss AD/AR 1
BSND Sensorineural deafness with mild renal dysfunction, Bartter syndrome AR 10 19
BTD Biotinidase deficiency AR 183 235
CABP2 Deafness AR 1 6
CACNA1D Primary aldosteronism, seizures, and neurologic abnormalities, Sinoatrial node dysfunction and deafness AD/AR 6 5
CCDC50 Deafness AD 1 4
CD151 Raph blood group BG 1
CDH23 Deafness, Usher syndrome AR/Digenic 69 332
CDKN1C Beckwith-Wiedemann syndrome, IMAGE syndrome AD 24 81
CEACAM16 Deafness AD 3 4
CHD7 Isolated gonadotropin-releasing hormone deficiency, CHARGE syndrome AD 192 784
CHSY1 Temtamy preaxial brachydactyly syndrome AR 6 11
CIB2 Deafness, Usher syndrome AR 4 15
CLDN14 Deafness AR 10 12
CLIC5 Deafness AR 1 1
CLRN1 Retinitis pigmentosa, Usher syndrome AR 17 34
COCH Deafness AD 10 28
COL2A1 Avascular necrosis of femoral head, Rhegmatogenous retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasia, Achondrogenesis type 2, Platyspondylic dysplasia Torrance type, Hypochondrogenesis, Spondyloepiphyseal dysplasia congenital (SEDC), Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, Kniest dysplasia, Spondyloperipheral dysplasia, Mild SED with premature onset arthrosis, SED with metatarsal shortening, Stickler syndrome type 1 AD 138 541
COL4A3 Alport syndrome AD/AR 34 229
COL4A4 Alport syndrome AD/AR 21 184
COL4A5 Alport syndrome XL 645 940
COL4A6 Deafness, with cochlear malformation XL 11 4
COL9A1 Stickler syndrome recessive type, Multiple epiphyseal dysplasia type 6 (EDM6) AR 7 5
COL9A2 Stickler syndrome, Multiple epiphyseal dysplasia type 2 (EDM2) AD/AR 7 12
COL9A3 Multiple epihyseal dysplasia type 3 (EDM3) AD/AR 6 15
COL11A1 Marshall syndrome, Fibrochondrogenesis, Stickler syndrome type 2 AD/AR 22 81
COL11A2 Weissenbacher-Zweymuller syndrome, Deafness, Otospondylomegaepiphyseal dysplasia, Fibrochondrogenesis, Stickler syndrome type 3 (non-ocular) AD/AR 23 54
CRYM Deafness AD 2 3
DCDC2 Deafness AR 9 9
DFNA5 Deafness AD 6 9
DFNB31 Deafness, Usher syndrome AR 11 30
DFNB59 Deafness AR 7 20
DIABLO Deafness AD 1 2
DIAPH1 Deafness AD 7 15
DIAPH3 Non-syndromic sensorineural deafness AD/AR 1 6
DLX5 Split-hand/foot malformation with sensorineural hearing loss AR 3 8
DSPP Dentin dysplasia, Dentinogenesis imperfecta, Deafness, with dentinogenesis imperfecta AD 9 47
EDN3 Hirschsprung disease, Central hypoventilation syndrome, congenital, Waardenburg syndrome AD/AR 6 21
EDNRB Hirschsprung disease, ABCD syndrome, Waardenburg syndrome AD/AR 7 66
ELMOD3 Deafness AR 1 1
EPS8 Deafness AR 1 2
ESPN* Deafness AD/AR 8 12
ESRRB Deafness AR 10 17
EYA1 Otofaciocervical syndrome, Branchiootic syndrome, Branchiootorenal syndrome AD 39 197
EYA4 Dilated cardiomyopathy (DCM) AD 9 24
FAM65B Deafness AR 1 2
FGF3 Deafness, congenital with inner ear agenesis, microtia, and microdontia AR 13 20
FGFR3 Lacrimoauriculodentodigital syndrome, Muenke syndrome, Crouzon syndrome with acanthosis nigricans, Camptodactyly, tall stature, and hearing loss (CATSHL) syndrome, Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia type 1, Thanatophoric dysplasia type 2, SADDAN AD/AR 53 70
FOXI1 Pendred syndrome, Enlarged vestibular aqueduct AR 1 9
GATA3 Hypomagnesemia, renal AD 20 77
GIPC3 Deafness AR 9 18
GJB2 Deafness, Bart-Pumphrey syndrome, Keratoderma, palmoplantar, with deafness, Vohwinkel syndrome, Hystrix-like ichthyosis with deafness, Keratitis-icthyosis-deafness syndrome AD/AR/Digenic 111 393
GJB3 Deafness AD/Digenic 10 38
GJB6 Deafness AR/Digenic 9 28
GPSM2 Deafness, Chudley-McCullough syndrome AR 14 11
GRHL2 Ectodermal dysplasia/short stature syndrome AD/AR 8 9
GRXCR1 Deafness AR 4 9
GRXCR2 Deafness AR 1 2
HARS Usher syndrome AR 5 9
HGF Deafness AR 4 10
HOMER2 Deafness AD 2
HOXB1 Facial paresis, hereditary congenital AR 1 5
HSD17B4 Perrault syndrome AR 41 96
ILDR1 Deafness AR 4 23
KARS Charcot-Marie-Tooth disease AR 7 20
KCNE1 Long QT syndrome, Jervell and Lange-Nielsen syndrome AD/AR/Digenic 8 45
KCNJ10 Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SESAME syndrome), Pendred syndrome, Enlarged vestibular aqueduct AR/Digenic 14 24
KCNQ1 Short QT syndrome, Long QT syndrome, Atrial fibrillation, Jervell and Lange-Nielsen syndrome AD/AR/Digenic 258 599
KCNQ4 Deafness AD 26 37
LHFPL5 Deafness AR 6 10
LOXHD1 Deafness AR 14 47
LRP2 Donnai-Barrow syndrome, Faciooculoacousticorenal syndrome AR 22 27
LRTOMT Deafness AR 7 16
MANBA Mannosidosis, lysosomal AR 12 18
MARVELD2 Deafness AR 7 17
MET Deafness, Renal cell carcinoma, papillary AD/AR 20 24
MIR96 Deafness AD 2 4
MITF Renal cell carcinoma with or without malignant melanoma, Tietz albinism-deafness syndrome, Waardenburg syndrome, Melanoma, cutaneous malignant AD 24 55
MSRB3 Deafness AR 4 2
MYH9 Sebastian syndrome, May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, Macrothrombocytopenia and progressive sensorineural deafness AD 21 113
MYH14 Deafness, Peripheral neuropathy, myopathy, hoarseness, and hearing loss AD 6 36
MYO1A Deafness AD 1 16
MYO3A Deafness AR 7 19
MYO6 Deafness AR 17 58
MYO7A Deafness, Usher syndrome AD/AR 155 426
MYO15A Deafness AR 66 221
NARS2 Combined oxidative phosphorylation deficiency AR 9 12
NDP Exudative vitreoretinopathy, Norrie disease XL 29 159
NLRP3 Neonatal onset multisystem inflammatory disease (NOMID), Muckle-Wells syndrome, Chronic infantile neurologic cutaneous articular (CINCA) syndrome AD 19 127
OSBPL2 Deafness AD 2 3
OTOA* Deafness AR 16 26
OTOF Neuropathy, Deafness AR 98 160
OTOG Deafness AR 6 3
OTOGL Deafness AR 16 19
P2RX2 Deafness AD 2 4
PAX3 Craniofacial-deafness-hand syndrome, Waardenburg syndrome AD/AR 22 135
PCDH15 Deafness, Usher syndrome AR/Digenic 71 107
PDZD7 Usher syndrome Digenic 1 15
PNPT1* Deafness AR 9 6
POLR1C Treacher Collins syndrome AR 16 20
POLR1D Treacher Collins syndrome AD/AR 7 26
POU3F4 Deafness XL 23 74
POU4F3 Deafness AD 8 31
PRPS1* Deafness, Phosphoribosylpyrophosphate synthetase I superactivity, Arts syndrome XL 22 27
PTPRQ Deafness AR 7 27
RDX* Deafness AR 6 8
RMND1* Combined oxidative phosphorylation deficiency AR 15 15
RPS6KA3 Coffin-Lowry syndrome, Mental retardation XL 47 165
SALL4 Acro-renal-ocular syndrome, Duane-radial ray/Okohiro syndrome AD 17 50
SEMA3E CHARGE syndrome AD 1 4
SERPINB6 Deafness AR 1 3
SIX1 Deafness, Branchiootic syndrome, Branchiootorenal syndrome AD 11 16
SIX5 Branchiootorenal syndrome AD 3 9
SLC17A8 Deafness AD 1 7
SLC19A2 Thiamine-responsive megaloblastic anemia syndrome AR 11 49
SLC26A4 Deafness, Pendred syndrome, Enlarged vestibular aqueduct AR 137 535
SLC26A5 Deafness AR 2 7
SLC29A3 Histiocytosis-lymphadenopathy plus syndrome, Dysosteosclerosis AR 16 23
SLC33A1* Congenital cataracts, hearing loss, and neurodegeneration AR 6 7
SLITRK6 Deafness and myopia AR 3 3
SMAD4 Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Polyposis, juvenile intestinal, Myhre dysplasia, Hereditary hemorrhagic telangiectasia AD 139 132
SMPX Deafness XL 7 12
SNAI2 Waardenburg syndrome AR 2 4
SOX10 Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease AD 34 133
STRC* Deafness AR 25 77
SUCLA2 Mitochondrial DNA depletion syndrome AR 8 27
SUCLG1 Mitochondrial DNA depletion syndrome AR 11 28
SYNE4 Deafness AR 4 1
TBC1D24 Deafness, Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome AD/AR 42 49
TCOF1 Treacher Collins syndrome AD 31 320
TECTA Deafness AD/AR 23 111
TFAP2A Branchiooculofacial sydrome AD 9 41
TIMM8A* Mohr-Tranebjaerg syndrome, Jensen syndrome, Opticoacoustic nerve atrophy with dementia XL 10 21
TJP2 Cholestasis, progressive familial intrahepatic, Hypercholanemia, familial AR 20 23
TMC1 Deafness AR 24 85
TMC2 Hearing loss AD/AR
TMEM132E Hearing loss AD/AR 1
TMIE Deafness AR 9 10
TMPRSS3 Deafness AR 23 79
TNC Deafness AD 3 3
TPRN Deafness AR 5 11
TRIOBP Deafness AR 17 35
TRMU Liver failure, infantile, Reversible infantile respiratory chain deficiency AR 18 17
TSPEAR Deafness AR 1 7
TYR* Albinism, oculocutaneous AR 69 391
USH1C Deafness, Usher syndrome AR 18 48
USH1G Usher syndrome AR 9 26
USH2A Usher syndrome, Retinitis pigmentosa AR 225 1001
VCAN Wagner disease AD 11 19
WFS1 Wolfram syndrome, Deafness AD/AR 65 343

*Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (; HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, The list of associated (gene specific) phenotypes are generated from CDG ( or Orphanet ( databases.

Gene Genomic location HG19 HGVS RefSeq RS-number
BCS1L Chr2:219525123 c.-50+155T>A NM_004328.4 rs386833855
CHD7 Chr8:61763035 c.5405-17G>A NM_017780.3 rs794727423
COL11A1 Chr1:103491958 c.781-450T>G NM_080629.2 rs587782990
COL4A5 ChrX:107838719 c.1424-20T>A NM_033380.2 rs281874668
COL4A5 ChrX:107813924 c.385-719G>A NM_033380.2 rs104886396
COL4A5 ChrX:107816787 c.466-17T>G NM_033380.2 rs104886415
COL4A5 ChrX:107938272 c.4821+121T>C NM_033380.2 rs104886423
COL4A5 ChrX:107938346 c.4822-151_4822-150insT NM_033380.2 rs397515494
GJB2 Chr13:20766921 c.-23+1G>A NM_004004.5 rs80338940
GJB2 Chr13:20766922 c.-23G>T NM_004004.5 rs786204734
GJB2 Chr13:20767159 c.-260C>T NM_004004.5
GRXCR1 Chr4:42965170 c.627+19A>T NM_001080476.2 rs201824235
KCNJ10 Chr1:160039811 c.-1+1G>T NM_002241.4 rs796052606
SLC26A4 Chr7:107301201 c.-103T>C NM_000441.1 rs60284988
SLC26A4 Chr7:107301305 c.-4+5G>A NM_000441.1 rs727503425
TIMM8A ChrX:100601671 c.133-23A>C NM_004085.3 rs869320666
USH2A Chr1:216247476 c.5573-834A>G NM_206933.2
USH2A Chr1:216064540 c.7595-2144A>G NM_206933.2 rs786200928
USH2A Chr1:216039721 c.8845+628C>T NM_206933.2

The strengths of this test include:

  • Blueprint Genetics is one of the few laboratories worldwide with CAP and ISO-15189 accreditation for NGS panels and CLIA certification
  • Superior sequencing quality
  • Careful selection of genes based on current literature, our experience and the most current mutation databases
  • Transparent and easy access to quality and performance data at the patient level that are accessible via our Nucleus portal
  • Transparent and reproducible analytical validation for each panel (see Test performance section; for complete details, see our Analytic Validation)
  • Sequencing and high resolution del/dup analysis available in one test
  • Inclusion of non-coding disease causing variants where clinically indicated (please see individual Panel descriptions)
  • Interpretation of variants following ACMG variant classification guidelines
  • Comprehensive clinical statement co-written by a PhD geneticist and a clinician specialist


This test does not detect the following:

  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Variants in regulatory or non-coding regions of the gene unless otherwise indicated (please see Non-coding disease causing variants covered by the panel). This mean for instance intronic variants locating deeper than 15 nucleotides from the exon-intron boundary.


This test may not reliably detect the following:

  • Low level mosaicism
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Disorders caused by long repetitive sequences (e.g. trinucleotide repeat expansions)


The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section and see our Analytic Validation.

Blueprint Genetics offers a Comprehensive Hearing Loss and Deafness Panel that covers classical genes associated with Alport syndrome, branchio-oto-renal (BOR) syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Mohr-Tranebjaerg syndrome, non-syndromic genetic deafness, Norrie disease, Pendred syndrome, sensorineural hearing loss, unilateral and bilateral, Stickler syndrome, treacher Collins syndrome, Usher syndrome and Waardenburg syndrome. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (, the NHLBI GO Exome Sequencing Project (ESP;, the Exome Aggregation Consortium (ExAC;, ClinVar database of genotype-phenotype associations ( and the Human Gene Mutation Database ( The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (, Polyphen (, and Mutation Taster (

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ 81430
DEL/DUP 81431

ICD codes

Commonly used ICD-10 codes when ordering the Comprehensive Hearing Loss and Deafness Panel

ICD-10 Disease
E70.30 Waardenburg syndrome
Q87.89 Alport syndrome
H90.5 Sensorineural hearing loss, unilateral and bilateral
E07.1 Pendred syndrome
H35.50 Usher syndrome
Q89.8 Stickler syndrome
Q87.89 Branchio-oto-renal (BOR) syndrome

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

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